Prevalence and impact of long COVID-19 among patients with diabetes and cardiovascular diseases in Bangladesh

Introduction Co-prevalence of long-COVID-19, cardiovascular diseases and diabetes is one of the major health challenges of the pandemic worldwide. Studies on long-COVID-19 and associated health outcomes are absent in Bangladesh. The main aim of this study was to determine the prevalence and impact of long-COVID-19 on preexisting diabetes and cardiovascular diseases (CVD) on health outcomes among patients in Bangladesh. Methods We collected data from 3,250 participants in Bangladesh, retrospectively. Multivariable logistic regression model was used to determine the odds ratio between independent and dependent variables. Kaplan-Meier survival curve was used to determine the cumulative survival. Results COVID-19 was detected among 73.4% (2,385 of 3,250) participants. Acute long-COVID-19 was detected among 28.4% (678 of 2,385) and chronic long-COVID-19 among 71.6% (1,707 of 2,385) patients. CVD and diabetes were found among 32%, and 24% patients, respectively. Mortality rate was 18% (585 of 3,250) among the participants. Co-prevalence of CVD, diabetes and COVID-19 was involved in majority of fatality (95%). Fever (97%), dry cough (87%) and loss of taste and smell (85%) were the most prevalent symptoms. Patients with co-prevalence of CVD, diabetes and COVID-19 had higher risk of fatality (OR: 3.65, 95% CI, 2.79–4.24). Co-prevalence of CVD, diabetes and chronic long-COVID-19 were detected among 11.9% patients. Discussion Risk of hospitalization and fatality reduced significantly among the vaccinated. This is one of the early studies on long-COVID-19 in Bangladesh.

Introduction: Co-prevalence of long-COVID-, cardiovascular diseases and diabetes is one of the major health challenges of the pandemic worldwide.Studies on long-COVID-and associated health outcomes are absent in Bangladesh.The main aim of this study was to determine the prevalence and impact of long-COVID-on preexisting diabetes and cardiovascular diseases (CVD) on health outcomes among patients in Bangladesh.
Methods: We collected data from , participants in Bangladesh, retrospectively.Multivariable logistic regression model was used to determine the odds ratio between independent and dependent variables.Kaplan-Meier survival curve was used to determine the cumulative survival.

. Introduction
In Bangladesh, COVID-19 have become one of the major public health concerns since the first report on March, 2020.COVID-19 has spread faster and affected people of all aspects in Bangladesh (1, 2).Nearly 2 038 129 people have been infected with COVID-19 and 29 446 deaths have been reported till April 24, 2023 in Bangladesh (3,4).About 88.5% of the total population of Bangladesh has received at least one dose and 48% got 3rd dose of vaccine (1, 3).Three peaks of COVID-19 pandemic have been identified in Bangladesh since 2020.One peak was apparently confined within the period of March, 2021 to May, 2021, and another one during June, 2021 to September, 2021 and the last one during January, 2022 to March, 2022 (3,4).Though vaccination is ongoing, breakthrough cases and variants with escape mutations are continuously contributing to the increase of cases of COVID-19 in Bangladesh.As of daily update on 24th April, 2023 the number of active cases were 10 197 and 254 of them had critical health conditions (3)(4)(5).
Studies on the prevalence of acute and chronic long-COVID-19 and their relation with pre-existing health conditions on the outcome are lacking in Bangladesh.Early studies on the impact of COVID-19 and comorbidities on the health outcome among patients in Bangladesh also suggest significant relationship of these health conditions.Therefore, we conducted this study to investigate the impact of long-COVID-19 among patients with diabetes and CVDs on health outcomes in Bangladesh.
. Materials and methods

. . Study design and population
A retrospective study was designed.Data was collected from 3,250 participants from seven divisions in Bangladesh during 01 January, 2022 and 31 December, 2022.The age of the participants ranged from 20 years to 78 years.According to the guidelines of the World Health Organization, the diagnosis was conducted by RT-PCR method (20).Data were collected in four sampling frames.Data on the report of hospitalization, ICU admission and discharge were collected directly from the patients and hospital authorities.Death reports were collected from the authorities and confirmed from the relatives of the patients.

. . Ethical approval
This study was ethically approved by the Biosafety, Biosecurity and Ethical Committee (BBEC) of Jahangirnagar University.Informed consent was taken from patients or relatives of the patients.The protocol number approved by the ethics committee is BBEC, JU/M 2021/COVID-19/(2)1.

. . Data collection
According to the guidelines of the World Health Organization, nasal or pharyngeal swab specimens were collected and used for the test in the hospitals/clinics (20).A positive outcome was defined by a positive laboratory test in the real-time reverse-transcriptase-PCR (RT-PCR) assay for SARS-CoV-2 and confirmed by high throughput sequencing (20).Data on the sociodemographic and economic conditions including sex, age, origin, monthly income, residing place, occupation, medical history, complication, treatment received (antiviral, antibiotic, steroid therapies, immune therapy, plasma therapy, respiratory support by mechanical ventilation and ICU support) were collected from the patients.Any pre-existing health conditions (defined by the International Classification of Diseases, 10th Revision, Clinical Modification), and outcome were included in this study (16,19).Data on the pre-existing health conditions including diabetes mellitus, cardiovascular disease (CVD), hypertension, hyperlipidemia, chronic obstructive pulmonary disease (COPD), malignancy, obesity and autoimmune disease were taken from the patients and examined by two experts.

. . Outcomes
The primary outcome was long time illness associated with COVID-19 infection.Secondary outcomes included hospitalization, admission to ICU, requirement of mechanical ventilation and fatality.Presence of chronic long-COVID-19 have worsened the clinical outcomes of pre-existing CVD, diabetes and COPD.Cardiovascular disease, malignant arrhythmia, diabetes and acute myocardial injury were defined based on the published works (16-19).

. . Statistical analyses
Percentage, rate and frequency were used for representing the categorical variables.Mean and standard deviation were used for representing central tendency of continuous variables.Independent sample t-tests were performed with 95% confidence intervals.P < 0.05 was considered statistically significant.The relationship between comorbidities and long COVID-19 were determined.Multivariable logistic-regression analysis was conducted to determine the impacts of sociodemographic factors and comorbidities on health outcome including fatality, hospitalization, ICU and long COVID-19.With 95% confidence intervals, adjusted odds ratios were determined.For the preexisting comorbidities, Charlson Comorbidity Index (CCI) were computed.We determined the Kaplan-Meier survival estimate by considering different age, sex, and comorbidities among patients with long COVID-19.All of the statistical analyses were performed by International Business Machines (IBM) Statistical Package for the Social Sciences (SPSS) version 28.0 (Chicago, IL, USA) and Microsoft Excel 2021.

. . Sociodemographic characteristics of the participants with COVID-
This study included 3,250 participants from seven divisions in Bangladesh.Nearly 73.4% (2,385 of 3,250) of the participants were COVID-19 positive.The mean (SD) age of the study population was 49 ± 3.6 years.Majority of the participants (66.5%) aged above 40 years (Table 1).The ratio of male to female was 2,340:910 (about 2.6:1).Majority of the participants (65.1%) were from semi-urban and rural areas with poor health facilities.About 96% of the population were from native Bangladeshi.Majority of the participants (68.9%) had a monthly income below 50,000 Bangladeshi taka (500 USD).The availability of health facility and effective treatment varied significantly on monthly income and place of residence in Bangladesh (Table 1).

. . Characterization of clinical symptoms and pre-existing health conditions
Clinical symptoms were analyzed by three physicians, recorded separately and compiled.Collected symptoms were cross-checked and evaluated for correction.Fever (97%, 2,313 of 2,385) was the most prevalent symptom followed by dry cough (87%, 2,074 of 2,385), loss of taste or smell (85%, 2,027 of 2,385), fatigue (81%, 1,932 of 2,385), sore throat (79%, 1,884 of 2,385), body aches (72%, 1,717 of 2,385), and chest pain or pressure (56%, 1,335 of 2,385), respectively (Figure 1A).Co-prevalence of multiple symptoms and duration of illness increased with increasing age among the patients.Reappearance of symptoms after 2 weeks of negative of COVID-19 infection were common among the participants (73.4%, 2,385 of 3,250).Male patients had two times greater risk of developing different symptoms associated with COVID-19 than female.

FIGURE (Continued)
Frontiers in Public Health frontiersin.org Frequency distribution of (A) di erent clinical symptoms in male and female, (B) di erent comorbidities in male and female patients with COVIDin Bangladesh, (C) distribution of clinical symptoms among patients with acute long-COVID-, (D) patients with chronic long-COVID-.Lines in each bar represented confidence intervals. .

. Survival rate analysis
Cumulative survival analysis of the study population was determined by using the Kaplan-Meier model.The cumulative survival rate of the participants was plotted against the time duration of survival or recovery.The analysis was conducted from week 0 to 25.The Kaplan-Meier model was applied for the data of the patients aged >40 years.We represented the findings for male and female separately.The cumulative survival rate of the male patients without COVID-19 remained above 0.5.Among female patients without COVID-19 the cumulative survival rate was also above 0.5.The cumulative survival rate gradually decreased to 0.0 in 24th week from 1.0 in 1st week among male patients with CVD, diabetes and COVID-19 (Figure 2).The cumulative survival rate among both male and female patients with COVID-19 decreased to 0.2 in the 24th week from 1 in the 1st week.Similarly, the survival rate among female patients with CVD, diabetes and COVID-19 was the lowest 0.1 in the 25th week.Male patients with CVD, diabetes and chronic long-COVID-19 had lower survival rate than female patients at the same time period (Figure 2).

. Discussion
The severity and longtime impact of the COVID-19 pandemic have adversely affected the global health system (8)(9)(10)(11).After the onset of the pandemic, it has remained one of the leading causes of global health burden among people.Among many health effects, post-COVID-19 sequelae in the infected is a major problem (11).In this study, we determine the prevalence of patients with acute long-COVID-19 and chronic long-COVID-19 in Bangladesh, and impact of COVID-19 on pre-existing cardiovascular disease and diabetes among them.We specified the predictors associated with poor health outcome, hospitalization, ICU admission and fatality among patients with COVID-19.We found that 73.4% of the participants were positive for COVID-19.About 28.4% of the patients were suffering from acute long-COVID-19 and 71.6% from chronic long-COVID-19 in Bangladesh.The prevalence of long COVID-19 reported in this study is higher than any of the previous studies (12)(13)(14)(15)(16)(17)(18)(19)(20).The probable reason might be the study cohort had pre-existing comorbidities, high prevalence of COVID-19, circulation of omicron variant (90%) during the study, and higher population density in the study regions.Nearly 29% of the patients had symptoms of COVID-19 for 13-24 weeks, 25.6% for 25-48 weeks and 17% for >48 weeks.These findings are one of the first reports of long COVID-19 in Bangladesh.The prevalence of COVID-19 is also high in this study compared to the previous studies (8-12, 16, 18-20).
We found that presence of COVID-19 contributed to the development of serious health outcome among patients with CVD and diabetes in Bangladesh.Majority of the fatality were associated with COVID-19, CVD and diabetes among the patients.However, we found lower fatality rate among the patients with chronic long-COVID-19 compared with patients with acute long-COVID-19.These findings are relatively new for data of Bangladesh.Presence of symptoms of COVID-19 for longer period and reappearance after certain time might affect the pre-existing CVD and diabetes.Studies have found that infection of COVID-19 have contributed to development of diabetes for certain period among the patients (16-19, [21][22][23][24][25][26][27][28].Further, studies have also reported that infection with COVID-19 might worsen the existing cardiovascular disease in patients.Certain medicines used to treat cardiovascular disease might have roles in poor health outcome among the COVID-19 patients (16,19,(24)(25)(26)(27)(28)(29)(31)(32)(33).Presence of previous CVD and diabetes increased the risk of poor health outcome and fatality rate after COVID-19 infection.Inversely, infection of COVID-19 has also triggered different adverse health impact in patients with CVD and diabetes.Previous studies have confirmed that COVID-19 infection has increased incidence of cardiac arrest, cardiomyopathy, myocardial infarction, and cardiac arrhythmias (13-19, 23, 26-33).
The main limitation of the study was the limited size of the population.Further, we could not include data on real-time hemoglobin A1c (HbA1c) and CVD disease conditions of the patients.Data on the clinical manifestations were missing for some of the patients and some of the data were self-reported.This is one of the first report of long-COVID-19 and associated health outcome in Bangladesh.In this study we reported high prevalence of chronic long-COVID-19 among patients in Bangladesh.Co-existence of CVD, diabetes and COVID-19 have significantly contributed to hospitalization, ICU admission and fatality among the participants.This study will add knowledge in understanding the long-time impact of COVID-19 and health burden of preexisting CVD and diabetes.Further, these findings will provide baseline data for future studies to reveal the exact mechanism of complicated health outcome and impact of COVID-19 among patients with CVD and diabetes.

FIGURE
FIGURECumulative survival rate among (A) male patients with CVD and COVID-, (B) female patients with CVD and COVID-, (C) male patients with diabetes and COVID-, (D) female patients with diabetes and COVID-, (E) male patients with CVD, diabetes and COVID-, (F) female patients with CVD, diabetes and COVID-in Bangladesh.